1. Field of the Invention
The present invention generally relates to methods and compositions that affect the GTP-binding activity of members of the Ras superfamily GTPases, along with uses for the compounds including methods of treating pathological conditions associated or related to a Ras superfamily GTPase.
2. Description of the Related Art
Rho family GTPases are molecular switches that control signaling pathways regulating cytoskeleton reorganization, gene expression, cell cycle progression, cell survival, and other cellular processes (Etienne-Manneville, 2002), which is incorporated herein by reference in its entirety.
Rho family proteins constitute one of three major branches of the Ras superfamily. Rho proteins share approximately 30 percent amino acid identity with the Ras proteins. At least 14 mammalian Rho family proteins have been identified thus far, including RhoA, RhoB, RhoC, RhoD, RhoE/Rnd3, Rnd1/Rho6, Rnd2/Rho7, RhoG, Rac1, Rac2, Rac3, Cdc42, TC10, and TTF.
Clinical trials have shown that antiplatelet therapy may significantly improve the care of patients with cardiovascular disease and stroke by blocking platelet deposition on the surface of damaged blood vessels. Aspirin, the most commonly used antiplatelet agent has limited usefulness because of the side effect of gastrointestinal bleeding and the fact that up to one-third of patients on chronic aspirin therapy develops aspirin resistance. Aspirin's irreversible effect on platelet function and long duration of action add to the inherent risk of bleeding associated with use of this drug. The thienopyridine derivative, clopidogrel has shown some effectiveness in the prevention of vascular events, but may have similar potential for severe side effects, such as thrombotic thrombocytopenic purpura, as the related drug ticlopidine. There has been very little experience with the thienopyridine derivative drugs in children. The more powerful parenterally-administered glycoprotein IIb/IIIa inhibitors abciximab, tirofibran and eptifibatide have had limited usefulness except in short-term clinical trials in conjunction with percutaneous interventional vascular repair and stenting in adults.